Transplantation of Human-Fetal-Spinal-Cord-Derived NPCs Primed with a Polyglutamate-Conjugated Rho/Rock Inhibitor in Acute Spinal Cord Injury

Cells, 2022 · DOI: 10.3390/cells11203304 · Published: October 20, 2022

Spinal Cord Injury Regenerative Medicine

Simple Explanation

Neural precursor cell (NPC) transplantation is a promising therapy for treating spinal cord injuries (SCIs). However, the clinical translation of this approach remains challenging due, in part, to the lack of consensus on an optimal cell source for human neuronal cells. The researchers used human-fetal-spinal-cord-derived NPCs (hfNPCs) from legal gestational interruptions at the late gestational stage, at 19–21.6 weeks. Before transplantation, they established a simple procedure to prime hfNPCs by overnight incubation with PGA-SS-FAS (at 50 µM FAS equiv.), which improved neuronal differentiation.

Study Duration

1 Month

Participants

Immune-deficient female NU (NCr)-Foxn1nu mice

Evidence Level

Not specified

Key Findings

1
In vitro, expanded hfNPCs retained neural features, multipotency, and self-renewal, which supported the development of a cell banking strategy.
2
PGA-SS-FAS priming signiﬁcantly increased neuronal differentiation (up to four-times the number of β-III-tubulin-positive neurons in comparison with non-primed control hfNPCs; 43.61 ± 4.92% vs. 9.85 ± 1.91) and promoted mature neuronal differentiation
3
PGA-SS-FAS-primed hfNPCs possessed enhanced grafting and migratory capacities and were encountered from the ventral to the dorsal areas of the spinal cord, while non-primed cells were restricted to the dorsal and injected areas.

Research Summary

Neural precursor cell (NPC) transplantation represents a promising therapy for treating spinal cord injuries (SCIs); however, despite successful results obtained in preclinical models, the clinical translation of this approach remains challenging due, in part, to the lack of consensus on an optimal cell source for human neuronal cells. We now conducted a similar study of human-fetal-spinal-cord-derived NPCs (hfNPCs) from legal gestational interruptions at the late gestational stage, at 19–21.6 weeks. Overall, the priming procedure using PGA-SS-FAS could represent an alternative methodology to improve the capabilities of the hfNPC lines for a translational approach for acute SCI treatment.

Practical Implications

Improved Cell Therapy

PGA-SS-FAS-primed hfNPCs provide a new combinatorial approach in a single formulation, which may serve as an improved cell therapy for SCI.

Enhanced Neuronal Differentiation

Priming with PGA-SS-FAS promotes faster cell maturation, favoring neuronal and oligodendroglial differentiation without interference with astroglial differentiation within 24 h of incubation.

Neuroprotection

Primed hfNPCs significantly preserved Tlx3- and Lbx1-expressing neuronal cells, which could be supported by the higher percentage of oligodendrocyte precursors induced by the treatment with PGA-SS-FAS prior to transplantation demonstrated in vitro.

Study Limitations

1
hfNPCs possessed a low amplification efficiency, with a PD time more than three-times the time needed for cell duplication when compared with other cell populations derived from earlier gestational stages
2
differences reported here, employing PGA-SS-FAS-primed hfNPCs, did not improve graft survival and did not improve functional regeneration
3
since an immune-deprived mouse model was employed hosting the exogenously transplanted human cells, further evaluation in an immune competent model will be needed to address the important limitation of the immune rejection prior to clinical application.

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